Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, 862-0973, Japan.
Pharm Res. 2009 Oct;26(10):2270-9. doi: 10.1007/s11095-009-9943-x. Epub 2009 Jul 25.
We recently developed prostaglandin E(1) (PGE(1))-encapsulated nanoparticles, prepared with a poly(lactide) homopolymer (PLA, Mw = 17,500) and monomethoxy poly(ethyleneglycol)-PLA block copolymer (PEG-PLA) (NP-L20). In this study, we tested whether the accelerated blood clearance (ABC) phenomenon is observed with NP-L20 and other PEG-modified PLA-nanoparticles in rats.
The plasma levels of PGE(1) and anti-PEG IgM antibody were determined by EIA and ELISA, respectively.
Second injections of NP-L20 were cleared much more rapidly from the circulation than first injections, showing that the ABC phenomenon was induced. This ABC phenomenon, and the accompanying induction of anti-PEG IgM antibody production, was optimal at a time interval of 7 days between the first and second injections. Compared to NP-L20, NP-L33s that were prepared with PLA (Mw = 28,100) and have a smaller particle size induced production of anti-PEG IgM antibody to a lesser extent. NP-L20 but not NP-L33s gave rise to the ABC phenomenon with a time interval of 14 days. NP-L33s showed a better sustained-release profile of PGE(1) than NP-L20.
This study revealed that the ABC phenomenon is induced by PEG-modified PLA-nanoparticles. We consider that NP-L33s may be useful clinically for the sustained-release and targeted delivery of PGE(1).
我们最近开发了包载前列腺素 E1（PGE1）的纳米粒，该纳米粒由一种聚乳酸均聚物（PLA，Mw=17500）和单甲氧基聚乙二醇-PLA 嵌段共聚物（PEG-PLA）（NP-L20）制备。在这项研究中，我们测试了 NP-L20 和其他聚乙二醇修饰的 PLA 纳米粒是否会在大鼠体内引发加速血液清除（ABC）现象。
通过 EIA 和 ELISA 分别测定 PGE1 的血浆水平和抗聚乙二醇 IgM 抗体。
NP-L20 的第二次注射比第一次注射从循环中清除得更快，表明 ABC 现象被诱导。这种 ABC 现象以及随之而来的抗聚乙二醇 IgM 抗体产生的诱导，在第一次和第二次注射之间 7 天的时间间隔最佳。与 NP-L20 相比，用 PLA（Mw=28100）制备且粒径较小的 NP-L33s 诱导产生的抗聚乙二醇 IgM 抗体程度较小。NP-L20 而不是 NP-L33s 在 14 天的时间间隔内引发 ABC 现象。NP-L33s 比 NP-L20 具有更好的 PGE1 持续释放特性。
本研究表明，ABC 现象是由聚乙二醇修饰的 PLA 纳米粒引发的。我们认为 NP-L33s 可能在临床上对 PGE1 的持续释放和靶向递送有用。
